Abused drugs-induce long-term behavioral disorders that are thought to be maintained by biological mechanisms in the central nervous system that are largely unknown. Work in this group during previous FYs has developed approaches to identify such genes and documented candidate genes whose expression are regulated by abused drugs, including amphetamine, cocaine and morphine. Several genes that can be readily identified as possible participants in neuronal signalling have been identified. These genes include that encoding a novel G protein beta subunit, a gene encoding a major regulated brain phosphoprotein phosphatase, calcineurin, and a gene encoding a novel G-protein-linked receptor. Functional implications of G-beta expression were sought using sense and antisense overexpression in neuroblastoma cells, and in vivo following intraventricular injection into experimental animals. Initial results reveal effects on neural process outgrowth in vitro and on cocaine-induced sensitization in vivo that are consistent with interesting possible roles for this G protein in the neuroadaptations that result from abused drug administration.